The objective of this proposal is to prepare monospecific antisera against human lymphoid cell surface antigens. Antigens specific for normal human thymus-dependent (T) and thymus-independent (B) lymphocytes and tumor-specific lymphoid antigens reactive with xenoantisera will be identified by biochemical and serological techniques. Cell hybrids between human T and B cell lines and a mouse lymphoma cell line will be prepared. Clones of cell hybrids, which have lost all but one of their human chromosomes and express only the human surface antigen of interest, will be selected by cloning out spontaneous variants or by cytotoxic immunoselection. These cells will then be used to immunize mice to give monospecific antisera against the human antigen. Since lymphoid antigens show a high degree of species specificity, attempts will be made to raise large quantities of effectively monospecific antisera against the human cell surface component by immunization of larger animals with the hybrid cells. The significance of this work lies in the new approach used to study human lymphocyte antigens in which biochemical, serological and somatic genetic techniques will be used in combination to achieve a depth of analysis not presently attained. The antisera produced will allow further detailed studies of normal and malignant human lymphocyte physiology to be carried out and may be useful as diagnostic or therapeutic reagents in human lymphoid diseases.